title: Occupational styrene exposure induces stress-responsive genes involved in cytoprotective and cytotoxic activities.
abstract: OBJECTIVE
  The aim of this study was to evaluate the expression of a panel of genes involved in toxicology in response to styrene exposure at levels below the occupational standard setting.
  
  
  METHODS
  Workers in a fiber glass boat industry were evaluated for a panel of stress- and toxicity-related genes and associated with biochemical parameters related to hepatic injury. Urinary styrene metabolites (MA+PGA) of subjects and environmental sampling data collected for air at workplace were used to estimate styrene exposure.
  
  
  RESULTS
  Expression array analysis revealed massive upregulation of genes encoding stress-responsive proteins (HSPA1L, EGR1, IL-6, IL-1β, TNSF10 and TNFα) in the styrene-exposed group; the levels of cytokines released were further confirmed in serum. The exposed workers were then stratified by styrene exposure levels. EGR1 gene upregulation paralleled the expression and transcriptional protein levels of IL-6, TNSF10 and TNFα in styrene exposed workers, even at low level. The activation of the EGR1 pathway observed at low-styrene exposure was associated with a slight increase of hepatic markers found in highly exposed subjects, even though they were within normal range. The ALT and AST levels were not affected by alcohol consumption, and positively correlated with urinary styrene metabolites as evaluated by multiple regression analysis.
  
  
  CONCLUSIONS
  The pro-inflammatory cytokines IL-6 and TNFα are the primary mediators of processes involved in the hepatic injury response and regeneration. Here, we show that styrene induced stress responsive genes involved in cytoprotection and cytotoxicity at low-exposure, that proceed to a mild subclinical hepatic toxicity at high-styrene exposure.
authors.affiliation: Department of Clinical and Molecular Sciences, Polytechnic University of Marche, Ancona, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Strafella
authors.forename: Massimo
authors.initials: M
authors.lastname: Bracci
authors.forename: Sara
authors.initials: S
authors.lastname: Staffolani
authors.forename: Nicola
authors.initials: N
authors.lastname: Manzella
authors.forename: Daniele
authors.initials: D
authors.lastname: Giantomasi
authors.forename: Matteo
authors.initials: M
authors.lastname: Valentino
authors.forename: Monica
authors.initials: M
authors.lastname: Amati
authors.forename: Marco
authors.initials: M
authors.lastname: Tomasetti
authors.forename: Lory
authors.initials: L
authors.lastname: Santarelli
mesh_terms: D000395:Air Pollutants, Occupational / Q000032:analysis*; D019610:Cytoprotection / Q000235:genetics*; D004797:Enzyme-Linked Immunosorbent Assay; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D005898:Glass; D006801:Humans; D007221:Industry; D015850:Interleukin-6 / Q000097:blood; D016014:Linear Models; D016273:Occupational Exposure; D060888:Real-Time Polymerase Chain Reaction; D012767:Ships; D013312:Stress, Physiological / Q000235:genetics*; D020058:Styrene / Q000032:analysis* / Q000097:blood / Q000633:toxicity / Q000652:urine; D011795:Surveys and Questionnaires; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D000395:Air Pollutants, Occupational; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; C009753:fiberglass; D020058:Styrene